Expression of circulating Semaphorin3A and its association with inflammation and bone destruction in rheumatoid arthritis

Gao, Hui; Ma, Xiaoxu; Guo, Qian; Xie, Lifeng; Zhong, Yuchao; Zhang, Xuewu

doi:10.1007/s10067-018-4070-x

Cited by 10 publications

(16 citation statements)

References 34 publications

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“…Additionally, Vadasz et al found that the serum levels of Sema3A were significantly lower in RA patients compared with those in the controls [ 51 ]. On the contrary, several studies reported that serum Sema3A levels were rather elevated in patients with inflammatory diseases including RA, as confirmed by our own results [ 52 – 54 ].…”

Section: Discussionsupporting

confidence: 89%

“…These conflicting results on the levels of secreted Sema3A may be due to small sample sizes and heterogeneous RA patients in individual studies. Vadasz et al enrolled only 24 RA patients and the study of Gao et al and ours did 130 patients with RA [ 51 , 52 ]. Also, measured expression levels of Sema3A could be different according to the sample types or detection methods.…”

Section: Discussionmentioning

confidence: 99%

“…Sema3A expression levels in CD4+/CD25+ T cells were significantly lower in patients with inflammatory bowel diseases than in controls, although their serum Sema3A levels were significantly higher [ 26 , 53 ]. Catalano reported that anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMC) expressed lower levels of Sema3A protein in RA patients than in controls, but Gao et al showed increased levels of its mRNA in RA PBMC [ 19 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

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Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis

Han

Kim

et al. 2018

Disease Markers

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Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p < 0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p = 0.001) and IL-6 (p < 0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p = 0.007) and TNF-α (p = 0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p = 0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p = 0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis

Han

Kim

et al. 2018

Disease Markers

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“…Discordant data have been reported regarding the expression and role of SEMA3A in RA. Decreased expression of SEMA3A has been shown to correlate with disease activity and the presence of histologic features of RA (29), which contrasts with the description of increased expression of Sema3A in RA patients, and has been shown to have a positive correlation with inflammatory factors, autoantibody production, and bone destruction (30). SEMA3A has been shown to induce the migration and invasive capacity of FLS (31), contrasting with the reduction in inflammation and progression of experimental autoimmune arthritis resulting from the administration of plasmid DNA encoding SEMA3A (32).…”

Section: Discussionmentioning

confidence: 97%

Semaphorins: From Angiogenesis to Inflammation in Rheumatoid Arthritis

Avouac

Pezet

Vandebeuque

et al. 2021

Arthritis & Rheumatology

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Objective To study the potential role of semaphorins in the pathogenesis of rheumatoid arthritis (RA). Methods Microarray experiments were performed on Affymetrix GeneChip Human Exon 1.0 ST arrays in RA endothelial cells (ECs) and control ECs derived from circulating progenitors. Expression of class 3 and class 4 semaphorins and their receptors in the serum of RA patients and healthy controls was assessed by immunohistochemical analysis in synovial tissue and by enzyme‐linked immunosorbent assay. Results Microarray analysis revealed differential expression of class 3 and class 4 semaphorins and their receptors in RA ECs. Semaphorin 4A (SEMA4A), plexin D1, and neuropilin 1 messenger RNA (mRNA) levels were markedly increased in RA ECs by 1.75‐, 2.21‐, and 1.68‐fold, respectively. Stimulation with tumor necrosis factor (TNF) led to a 2‐fold increase in SEMA4A mRNA levels in RA ECs, and deficient SEMA4A expression modified RA EC angiogenic properties. Class 3 and class 4 semaphorins as well as their receptors were overexpressed in RA synovial tissue. A respective 1.30‐fold increase and 1.54‐fold increase in SEMA4A and SEMA3E, as well as a 24% decrease in SEMA3A, was observed in the serum of RA patients. Serum levels of SEMA4A, SEMA4D, and SEMA3A correlated with levels of inflammation and proangiogenic markers. In 2 independent cohorts of patients with low disease activity or with RA in remission, the presence of SEMA4A identified patients with residual disease activity. Conclusion Gene expression profiling of ECs identified class 3 and class 4 semaphorins as potential biomarkers and therapeutic candidates in RA, with confirmed overexpression in ECs, synovial vessels, and serum, and correlation with validated markers of inflammation and angiogenesis. Thus, semaphorins might be novel and appealing EC‐derived inflammatory and proangiogenic targets in RA.

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“…It was correlated with RF, immunoglobulin M (IgM), ESR, platelet counts, lumbar spine bone mineral density (BMD), and the Sharp score. The optimal diagnostic cutoff value of 10.881 ng/ml for Sema3A was based on the receiver operating characteristic (ROC) curve ( 63 ). In addition, ribophorin-II (RPN2) mRNA expression was significantly upregulated in the PBMCs of RA patients in a case–control study sample.…”

Section: Candidate Rnas As Biomarkers For Ramentioning

confidence: 99%

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

Jiang

Zhong

et al. 2023

Front. Immunol.

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In recent years, diagnostic and therapeutic approaches for rheumatoid arthritis (RA) have continued to improve. However, in the advanced stages of the disease, patients are unable to achieve long-term clinical remission and often suffer from systemic multi-organ damage and severe complications. Patients with RA usually have no overt clinical manifestations in the early stages, and by the time a definitive diagnosis is made, the disease is already at an advanced stage. RA is diagnosed clinically and with laboratory tests, including the blood markers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and the autoantibodies rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA). However, the presence of RF and ACPA autoantibodies is associated with aggravated disease, joint damage, and increased mortality, and these autoantibodies have low specificity and sensitivity. The etiology of RA is unknown, with the pathogenesis involving multiple factors and clinical heterogeneity. The early diagnosis, subtype classification, and prognosis of RA remain challenging, and studies to develop minimally invasive or non-invasive biomarkers in the form of biofluid biopsies are becoming more common. Non-coding RNA (ncRNA) molecules are composed of long non-coding RNAs, small nucleolar RNAs, microRNAs, and circular RNAs, which play an essential role in disease onset and progression and can be used in the early diagnosis and prognosis of RA. In this review of the diagnostic and prognostic approaches to RA disease, we provide an overview of the current knowledge on the subject, focusing on recent advances in mRNA–ncRNA as diagnostic and prognostic biomarkers from the biofluid to the tissue level.

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Expression of circulating Semaphorin3A and its association with inflammation and bone destruction in rheumatoid arthritis

Cited by 10 publications

References 34 publications

Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis

Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis

Semaphorins: From Angiogenesis to Inflammation in Rheumatoid Arthritis

Biomarkers (mRNAs and non-coding RNAs) for the diagnosis and prognosis of rheumatoid arthritis

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